The activity of proteolytic enzymes in the soluble proteins of rat and human lenses may be related to cataractogenesis. During cataract formation, the amount of protein in the lens decreases, and the relative amounts of the crystallin fractions change. The soluble proteins of the normal and cataractous rat lens have been fractionated and characterized in our laboratory. Microscale procedures have been developed that permit biochemical analysis of sections of the lens containing 1 mg protein. Using these techniques and others we will study the proteolytic enzymes associated with the lens soluble proteins. This will involve determining the types of proteolytic enzymes present, the in vivo substrates, and the distribution of proteolytic activity in the lens. The biochemical findings will be correlated with the three dimensional ultrastructure of the lens analyzed by scanning electron microscopy. An understanding of how proteins are changed is essential for the complete elucidation of the mechanism of cataractogenesis.